The effects of malnutrition on the prenatal development of rat brain]

Female rats were submitted to caloric and protein restriction 8 days before fecondation and during pregnancy. A reduction of the number of brain cells in the fetuses was evident only after the 20th day of pregnancy. This reduction appeared to be limited to glial cells, and not to affect neurons contrarily to what had previously been stated by some authors.     

The effect of low-level prenatal X-irradiation on postnatal development in the Wistar rat

The objective of this investigation was to determine the effect of low-dose prenatal X-irradiation on postnatal growth and neurobehavioral development, and whether alterations would manifest at dosages lower than those which produce anatomic malformations from exposure at the most sensitive period of organogenesis. Ninety-eight Wistar strain rats were exposed to 0.1, 0.2, or 0.4 Gy X-radiation of were sham irradiated on the 9th or 17th day of gestation. A conventional teratologic evaluation was completed on half of the animals (572 fetuses). The age of appearance of four physiologic markers and of acquisition of six reflexes was observed in 372 offspring. Exposure during early organogenesis at these levels had no effect on any of these parameters. Prenatal exposure to X-radiation on the 17th day of gestation at dosage levels greater than 0.1 Gy resulted in alterations in the appearance of three postnatal neurophysiologic parameters. Growth retardation throughout the postpartum period also was observed in the offspring. The induction of developmental and reflex alterations had a comparable threshold to the known threshold for anatomic malformations on the 9th day. These results indicate that all of the parameters studied had thresholds either at or above 0.2 Gy acute radiation, and that the postpartum developmental and reflex acquisition measures were not more sensitive indicators of exposure to X-radiation than growth parameters.     

The effect of corticosteroids on dendritic development in the rat brain

Sprague-Dawley rats were given 0.02 ml of methylprednisolone (0.06 g/g body wt) 6, 9, or 12 days postnatally. When compared with saline-treated controls, the following effects on dendritic development in layers 3 and 5 of the parietal cortex were observed: (1) no significant alteration in number of basal dendrites; (2) initial increase (at 3 wk of age) in branchings near the perikaryon in the group treated at 12 days; (3) decrease in number of branches at distances ≥270 μm from the perikaryon in layers 3 and 5 in all steroid-treated groups when sacrificed at 6 wk; (4) decrease in number of intersections in layer 5 in all steroid-treated groups when sacrificed at 6 wk; and (5) decrease in number of terminations in layers 3 and 5 in all steroid-treated groups when sacrificed at 6 wk.     

The effect of trichlorfon and other organophosphates on prenatal brain development in the guinea pig

The organophosphates trichlorfon, dichlorvos, dimethoate, soman, triortho-cresyl phosphate (TOCP), and the diethoxy-analogue of trichlorfon (O,O-diethyl 2,2,2-trichloro-1-hydroxyethylphosphonate, ethyl-trichlorfon), were administrated to guinea pigs between day 42 and 46 of gestation. When the offsprings were examined at birth, there was a severe reduction in brain weight in the case of trichlorfon and dichlorvos, but not after treatment with the other organophosphates. The reduction in weight was most pronounced for cerebellum, medulla oblongata, thalamus/hypothalamus and quadrigemina. The effect was less marked for cerebral cortex and hippocampus. Since soman, a potent anticholinesterase, and TOCP, an inhibitor of neuropathy target esterase, did not show any effects, this excludes that the brain hypoplasia can be caused by inhibition of these two enzymes. Further, the lack of effect with ethyl-trichlorfon has shed some light on the part of the trichlorfon molecule which could be involved in the formation of the hypoplasia. It is suggested that alkylation of DNA may be involved in the development of the lesion. The possible consequences for a teratogenic effect of trichlorfon and dichlorvos on humans are discussed.Special issue dedicated to Dr. Bernard W. Agranoff.     

Cross-generational effect of prenatal morphine exposure on neurobehavioral development of rat pups

Prenatal exposure to opiates can have devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. The present study was aimed at identifying cross-generational effects of prenatal morphine exposure in Sprague-Dawley rats. Pregnant rats were injected subcutaneously with either saline or morphine (10 mg/kg) twice daily during gestational days 11-18. Litter size, percentage of males and females, anogenital distances (AGDs), righting reflex, and body weight were assessed in prenatally morphine-exposed pups (first generation) and their offspring (second generation). Both prenatally morphine-exposed pups and offspring of prenatally morphine-exposed dams exhibited an increased latency to right. Additionally, second generation pups were slower in righting than first generation pups. During the early postnatal period the second generation pups weighed less than the first generation regardless of drug exposure. The AGDs of second generation male pups were decreased relative to the first generation. Our data provide important novel information about the trans-generational effects of maternal opiate abuse that may be useful for understanding/evaluating the teratogenic effects of prenatal opiate exposure.     

The effect of steroid treatment on lipocortin immunoreactivity of rat brain

Lipocortin-1, lipocortin-2 and lipocortin-5 were immunohistochemically assessed in rats. Apart from animals receiving no treatment, other animals received pretreatment with methylprednisolone, or the 21-aminosteroid U-74389F. Whereas Hpocortin immunoreactivity was absent in the greater part of the brain in animals not pretreated with steroid (except in sporadic microglial cells and choroid plexus), there was obvious immunostaining of parenchymatous elements in steroid pretreated animals. In the steroid pretreated animals lipocortin immunoreactivity of the brain tissue may indicate local formation of lipocortin under the influence of steroids that had entered the tissue. The cellular elements which showed immunostaining included meningeal cells, neurones, ependyma, oligodendroglia and capillary endotheHum.     

The prenatal development of alkaline phosphatase activity in the hypothalamus of the rat

The localization of alkaline phosphatase (E.C. 3.1.3.1.) positivity during prenatal development of the hypothalamus of the rat is described. At E12 all layers of the prosencephalon display alkaline phosphatase (AP) positivity. The AP positivity increases from dorsal to ventral. Within the hypothalamic area a second, rostro-ventral gradient exists from E14 onwards. At E18 both gradients have decreased. At E20 almost all AP positivity has disappeared from the hypothalamus, with the exception of some reaction product in the dorsal ventricular matrix of the hypothalamus. The significance of this pattern in relation to the differentiation of the hypothalamus and to the formation of hypothalamic connections is discussed. It is suggested that AP activity is related to the formation of connections.     

The effect of chronic stress on prenatal development of the central nervous system

Abstract

The survival of developing embryos depends on the control and maintenance of homeostasis. Stress caused by chronic immobilization during pregnancy in rats may alter the normal development of the nervous system and increase susceptibility to psychiatric disorders. We investigated the effects of chronic stress on cell proliferation in the forebrains of embryos at 12 days of gestation, and in the hippocampus, dentate gyrus and cortex in embryos at 17 and 21 days of gestation. We examined serial sections of the embryonic brains of control and stressed rats at days 12, 17 and 21 of gestation. Brain sections were immunolabeled with anti-PCNA and stereological analysis was performed on 540 images. The results showed no statistical differences on days 12 and 17 of gestation in the proliferation area of the structures studied, whereas on day 21 of gestation, proliferation decreased in the cortex and dentate gyrus of embryos of the stressed group. These changes were related to decreased prolactin and increased corticosterone concentrations in the plasma.     

Effects of chemically induced maternal toxicity on prenatal development in the rat

The hypothesis that chemically induced overt maternal toxicity induces a characteristic syndrome of adverse developmental effects in the rat was investigated. Pregnant animals (Sprague-Dawley strain) were dosed by oral gavage with one of a series of compounds on days 6-15 of gestation. These chemicals were diquat (DIQ), ethylene-bis-isothiocyanate (EBIS), toxaphene (TOX), styrene (STY), 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenol (2,4,5-Tr), triphenyl tin hydroxide (TPTH), and cacodylic acid (CAC). The compounds were chosen because they exhibited little or no developmental toxicity in previous studies. Dosage levels producing maternal weight loss and/or lethality were determined from preliminary toxicity studies. Significant maternal weight reductions were noted during the course of treatment with all compounds except CAC and 2,4,5-Tr. Maternal lethality was produced by EBIS, TOX, 2,4,-D, and 2,4,5-Tr. The main treatment-related developmental toxicity noted in litters at term consisted of increased lethality (EBIS, TPTH) and decreased fetal weight (EBIS and CAC). Treatment-related anomalies were seen in litters treated with 2,4-D and TOX (supernumerary ribs) and with EBIS and STY (enlarged renal pelvis). No significant developmental effects were produced with DIQ, or 2,4,5-Tr. This study indicates that overt maternal toxicity as defined by weight loss or mortality is not always associated with the same defined syndrome of adverse developmental effects in the rat.     

The effect of phenylpyruvate on pyruvate metabolism in rat brain

1. The effect of phenylalanine and phenylpyruvate on the metabolism of pyruvate by isolated mitochondria from rat brain was investigated. 2. Phenylpyruvate inhibited the fixation of H(14)CO(3) (-) in the presence of pyruvate by intact rat brain mitochondria, whereas phenylalanine and other metabolites of this amino acid had no inhibitory effect on this process. 3. Pyruvate carboxylase activity in freeze-dried rat brain mitochondrial preparations was also inhibited only by phenylpyruvate, and a ;mixed type' inhibition was observed. 4. The K(m) for pyruvate of rat brain pyruvate carboxylase was about 0.2mm. 5. The concentration of phenylpyruvate required for a 50% inhibition of H(14)CO(3) (-) fixation by the intact mitochondria and of pyruvate carboxylase activity was dependent on the concentration of pyruvate used in the incubation medium. 6. The possible significance of inhibition of pyruvate carboxylase activity by phenylpyruvate in the brains of phenylketonuric patients is discussed.